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  • Title: A role for apoptosis-inducing factor in T cell development.
    Author: Banerjee H, Das A, Srivastava S, Mattoo HR, Thyagarajan K, Khalsa JK, Tanwar S, Das DS, Majumdar SS, George A, Bal V, Durdik JM, Rath S.
    Journal: J Exp Med; 2012 Aug 27; 209(9):1641-53. PubMed ID: 22869892.
    Abstract:
    Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T cell receptor β recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding-deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity-deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic β-selection.
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